Value In Pathology Research Articles

Mechanical Microvibration Device Enhancing Immunohistochemistry Efficiency.

Immunohistochemistry (IHC) is a widely used technique in diagnostic pathology and biomedical research, but there is still a need to shorten the operation process and reduce the cost of antibodies. This study aims to assess a novel IHC technique that incorporates mechanical microvibration (MMV) to expedite the process, reduce antibody consumption, and enhance staining quality. MMV was generated using coin vibration motors attached to glass slides mounted with consecutive tissue sections. Multiple antibodies targeting various antigens were used to stain cancerous and normal tissues, with and without microvibration. Various parameters were tested, including incubation durations, temperatures, and antibody dilutions. The novel method showed the potential to achieve comparable or superior outcomes in significantly less time, utilizing over 10 times less antibody than controls. MMV improved specific staining quality, yielding stronger, and better-defined positive reactions. This was validated through a multicenter double-blind assessment and quantitative image analysis. The possible mechanisms were also investigated. MMV shortens immunohistochemical staining duration, reduces antibody usage, and enhances staining specificity, likely by accelerating antibody movement and diffusion. These improvements translate to time and cost savings, offering clinical and financial value for diagnostic pathology and biomedical research.

Prevalence and predictors of right ventricular dysfunction among adults living with HIV in northwest Nigeria.

People living with the human immunodeficiency virus (PLWH) are at increased risk of cardiovascular diseases. Right ventricular (RV) function has important prognostic value in cardiac pathology, and advances in imaging modalities, such as transthoracic echocardiography have enabled in-depth RV studies. There is, however, a scarcity of multiparameter RV function studies in PLWH in low- and middle-income settings, such as Nigeria. The aim of this study is to determine the prevalence and predictors of RV dysfunction among adult PLWH in northwest Nigeria. This is a retrospective cross-sectional study conducted between February 1, 2023 and August 31, 2023. We consecutively recruited 330 adults [median age 45 years, interquartile range (IQR), 38 to 52 years, 61% female] attending human immunodeficiency virus (HIV) and general outpatient clinics in a tertiary hospital in northwest Nigeria. They included 110 antiretroviral therapy (ART)-experienced PLWH, 110 ART-naïve PLWH, and 110 age- and sex-matched HIV-negative control subjects. All participants had conventional two-dimensional (2D), tissue Doppler (TDI), and speckle tracking (2D-STE) echocardiography to estimate left ventricular (LV) and RV systolic and diastolic function, peak systolic and diastolic myocardial velocities, RV and LV longitudinal strain, and chamber dimensions. All participants also underwent 12-lead electrocardiography. Multiple linear and Firth's logistic regression modeling were performed to assess for independent predictors of RV myocardial performance index (RVMPI) as a continuous and as a dichotomous variable, respectively. The prevalence of RV dysfunction, as determined by the RVMPI among HIV-positive participants was 14.5% [95% confidence interval (CI): 10.5-19.8%] compared to 0% (95% CI: 0.0-3.4%) for those without HIV. Among participants with HIV, RVMPI was associated with participant age (P<0.001) and left ventricular ejection fraction (LVEF) (P<0.001). Results were similar when RVMPI was dichotomized. The association between RV dysfunction and LVEF was modified by ART status: a 10% decrease in LVEF was associated with an average decrease of 0.08 in RVMPI among participants who were ART-experienced (β=-0.08, P<0.001) but a lesser decrease among those who were ART- naïve (β=-0.03, P=0.14). This study highlights the complexity of RV dysfunction in PLWH and underscores the importance of LVEF and age as key factors influencing the risk of RV dysfunction in PLWH.

Local extension findings on MRI compensate for the ability of pathological staging to predict oncological outcome.

We investigated whether local extension findings on preoperative MRI and excisional pathology are associated with positive surgical margin and biochemical recurrence after robot-assisted radical prostatectomy. We identified 704 of our patients that underwent robot-assisted radical prostatectomy between 2012 and 2020, and extracted the 326 patients who had preoperative MRI scans and a radiologist reading. These patients were classified into groups according to the presence of local extension on MRI and pathological findings: ≤ cT2pT2 (195 cases), ≤ cT2pT3 (55 cases), cT3pT2 (31 cases), and cT3pT3 (45 cases). We compared positive surgical margin and biochemical recurrence between them. Median age was 69years, positive surgical margin rate was 20.2%, and five-year biochemical recurrence rate was 20.3%. Of the 226 patients without local invasion on excisional pathology, those with local extension on MRI (cT3pT2) had relatively higher positive surgical margin rate (29.0% vs. 14.4%, p = 0.05) and significantly higher five-year biochemical recurrence rate (25.8% vs. 9.3%, p = 0.01) than those without local extension on MRI (≤ cT2pT2). Similarly, among the 100 patients with local extension on excisional pathology, those with cT3pT3 had relatively higher positive surgical margin (37.8% vs. 21.8%, p = 0.08) and significantly higher five-year biochemical recurrence (53.3% vs. 29.3%, p = 0.01) than those with ≤ cT2pT3. In multivariate analysis, local extension on MRI was an independent predictor of biochemical recurrence (OR 2.1, 95%CI 1.1-3.9, p = 0.01). Local extension on MRI is a prognostic factor independent of pathological stage. The use of MRI may complement the prognostic value of excisional pathology of prostate cancer.

18FFlutemetamol-PET Aided Classification of Cerebral Amyloid Angiopathy: A Multicenter Study.

Cerebral amyloid angiopathy (CAA)-related features on neuroimaging often coexist with signs of arteriolosclerosis-small vessel disease on neuroimaging in people with intracranial hemorrhage (ICH). This study aimed at defining the value of amyloid pathology detected by 18Fflutemetamol PET in reclassification and stratification of risk of bleeding in people with mixed CAA-arteriolosclerosis features. We included consecutive patients admitted to 2 institutions (2018-2023) with spontaneous symptomatic ICH, subarachnoid hemorrhage (SAH), transient focal neurologic episodes (TFNE), or cognitive impairment and MRI showing CAA hallmarks. All patients underwent brain magnetic resonance imaging (MRI) with susceptibility weighted imaging and 18Fflutemetamol PET imaging and were followed up for at least 1 year. We compared cases with CAA and arteriolosclerosis + CAA features and defined long-term outcomes (composite outcome including death, ICH, ischemic stroke, SAH, TFNE) depending on PET status (CAA/amyloid pathology vs arteriolosclerosis-predominant groups). Among 47 patients, according to PET and MRI imaging, 38 patients were reclassified in the CAA/amyloid pathology group and 9 in the arteriolosclerosis-predominant group, with similar cardiovascular risk factors but a significantly higher lobar microbleed burden for the former group. The CAA/amyloid pathology group had higher rates of composite outcome (43.9 vs 11.1 events per 100 patient-year; p = 0.039) and ICH (36.5 vs 5.6 events per 100 patient-years; p = 0.04) compared with the arteriolosclerosis-predominant group. 18FFlutemetamol PET imaging can help in reclassification of mixed arteriolosclerosis + CAA into CAA/amyloid pathology and arteriolosclerosis-predominant, with implications on long-term risk of recurrent events. This study provides Class IV evidence that 18Fflutemetamol PET can distinguish between CAA + arteriolosclerosis and arteriolosclerosis-predominant pathology.

Multi-parametric MRI-based machine learning model for prediction of pathological grade of renal injury in a rat kidney cold ischemia-reperfusion injury model

BackgroundRenal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier.ObjectiveTo evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach.MethodsEighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading.ResultsAll rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90).ConclusionThe multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

FDG-PET associations with pathological response and survival with neoadjuvant immunotherapy for melanoma.

9523 Background: This study sought to describe the changes seen with FDG-PET following neoadjuvant immunotherapy in melanoma patients (pts), and explore associations with pathological response and recurrence-free survival (RFS). Methods: Two prospective clinical trial cohorts of stage III pts with RECIST measurable nodal melanoma were included; 1) NeoTrio, 13 pts received 2 doses of preoperative pembrolizumab alone, and 2) NeoPele, 20 pts received 2 doses of pembrolizumab and 5 weeks of lenvatinib preoperatively. All pts underwent baseline and week 6 (preoperative) FDG-PET assessments and all had surgery. PET responses were evaluated based on the modified EORTC criteria. In addition to the standard categories Complete Metabolic Response (CMR), Partial Metabolic Response (PMR), Stable Metabolic Disease (SMD), and Progressive Metabolic Disease (PMD), a novel category was established, near-CMR, where the maximum standardized uptake value (SUVmax) decreased by more than 90%. PET responses were determined while blinded to the outcome data. Pathological response was determined as per INMC criteria. Results: 33 pts were included, 67% male, median age 65 years, 48% BRAF mutant. Pathological response, PET response and correlations are shown in the Table. All 8 (24%) pts achieving CMR or near-CMR obtained major pathologic response (MPR), while the 14 pts (42%) with PMR had variable pathological outcomes (57% MPR, 21% pPR, 21% pNR). For the 6 pts with PMD, 5 (83%) had pNR and the one pts who achieved pCR recurred with brain metastases. After a median 29.9 mo follow-up (95% CI 27.0-33.1), PET response associated with RFS; those with CMR/near CMR had 100% 24mo RFS (nil recurrences to date) while those with PMR or SMD had inferior survival (79% and 80% 24mo RFS), and those with PMD the worst outcomes (17% 24mo RFS, all pts except one have recurred) (p=0.0029). The predictive value of PET and pathology for RFS was assessed using the Cox Proportional Hazards model. 12- and 24-month RFS AUCs of PET and pathology response were similar at 81.5% (95% CI: 67.7-95.3) vs. 80.9% (95% CI: 67.8-93.9), and 83.3% (95% CI: 69.1-97.5%) vs. 80.8% (95% CI: 66.6-94.9), respectively. Conclusions: FDG-PET demonstrates utility in predicting pathological response and survival with neoadjuvant immunotherapy in melanoma. PET may identify pts who are not going to be pathological responders and who have the worst survival outcomes, enabling a potential switch of neoadjuvant systemic therapy. [Table: see text]

Direct three-dimensional segmentation of prostate glands with nnU-Net.

In recent years, we and others have developed non-destructive methods to obtain three-dimensional (3D) pathology datasets of clinical biopsies and surgical specimens. For prostate cancer risk stratification (prognostication), standard-of-care Gleason grading is based on examining the morphology of prostate glands in thin 2D sections. This motivates us to perform 3D segmentation of prostate glands in our 3D pathology datasets for the purposes of computational analysis of 3D glandular features that could offer improved prognostic performance. To facilitate prostate cancer risk assessment, we developed a computationally efficient and accurate deep learning model for 3D gland segmentation based on open-top light-sheet microscopy datasets of human prostate biopsies stained with a fluorescent analog of hematoxylin and eosin (H&E). For 3D gland segmentation based on our H&E-analog 3D pathology datasets, we previously developed a hybrid deep learning and computer vision-based pipeline, called image translation-assisted segmentation in 3D (ITAS3D), which required a complex two-stage procedure and tedious manual optimization of parameters. To simplify this procedure, we use the 3D gland-segmentation masks previously generated by ITAS3D as training datasets for a direct end-to-end deep learning-based segmentation model, nnU-Net. The inputs to this model are 3D pathology datasets of prostate biopsies rapidly stained with an inexpensive fluorescent analog of H&E and the outputs are 3D semantic segmentation masks of the gland epithelium, gland lumen, and surrounding stromal compartments within the tissue. nnU-Net demonstrates remarkable accuracy in 3D gland segmentations even with limited training data. Moreover, compared with the previous ITAS3D pipeline, nnU-Net operation is simpler and faster, and it can maintain good accuracy even with lower-resolution inputs. Our trained DL-based 3D segmentation model will facilitate future studies to demonstrate the value of computational 3D pathology for guiding critical treatment decisions for patients with prostate cancer.

MRI findings of peroneal tendon tears do not necessarily correlate to clinical findings in paediatric and adolescent patients.

Pathologic abnormality of the peroneal tendons are thought to be an under-appreciated source of vague ankle and hindfoot pain in paediatric patients, partly because they can be difficult to diagnose and differentiate from lateral ankle ligament injuries. While magnetic resonance imaging (MRI) is the primary imaging modality used to detect peroneal tendon pathology, previous studies in adults have found that positive MRIs demonstrate a positive predictive value (PPV) of associated clinical findings around 48%. There are no similar known published studies in the paediatric population. Our objective was to determine the positive predictive value of peroneal tendon pathology as diagnosed by MRI as related to positive clinical exam findings in the paediatric and adolescent population. This IRB approved retrospective study was conducted at a tertiary children's hospital. Inclusion criteria included patients under 18years from our tertiary care institution with (a) ankle MRI findings indicating pathology of the peroneus brevis/longus tendons confirmed by a board certified paediatric musculoskeletal radiologist and (b) formal review of the clinical examination by a fellowship trained paediatric orthopaedic surgeon. Patients with congenital deformities or previous surgical intervention of the lateral ankle were excluded. Forty-seven patients (with 48 MRIs) met inclusion criteria over a tenyear period. The majority of the positive MRI scans (70%) demonstrated a peroneus brevis split tear. Of the patients with positive findings on MRI, 17 patients had an associated positive clinical exam. The positive predictive value of MRI for peroneal tendon tears with positive clinical findings was 35.41% (95% confidence interval = 31.1% to 41.6%). There were 31 patients with MRI positive findings with a negative clinical exam. Despite having a negative clinical exam, a high percentage of patients had positive MRI findings suggestive of peroneal tendon pathology which confirms findings of adult populations demonstrating a high rate of incidental finding of peroneal tendon pathology on MRI in paediatric patients.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study.

Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Liver allograft pathology in the late post-transplant period

Annually increasing quantity of liver transplants and the growing population of long-survived recipients determine the relevance of late allograft dysfunction study. Variety of morphological and functional disorders of the transplanted liver complicates their timely diagnostics. Moreover, in some patients, serious graft damage may proceed for a long time without clinical manifestations and laboratory abnormalities.The review summarizes the structure, prevalence, risk factors and prognostic value of different liver allograft pathology determined by histological examination in the long term after transplantation.

Decision system for extent of resection in WHO grade 3 gliomas: a Chinese Glioma Genome Atlas database analysis.

Extensive surgical resection has been found to be associated with longer survival in patients with gliomas, but the interactive prognostic value of molecular pathology of the surgical resection is unclear. This study evaluated the impact of molecular pathology and clinical characteristics on the surgical benefit in WHO grade 3 IDH-mutant gliomas. Clinical and pathological information of 246 patients with WHO grade 3 IDH-mutant gliomas were collected from the Chinese Glioma Genome Atlas database (2006-2020). The role of the extent of resection on overall survival, stratified by molecular pathology and clinical characteristics, was investigated. We then assessed prognostic factors using a univariate log-rank test and multivariate Cox proportional hazards model in the subgroups. The extent of resection was an independent prognostic factor in the entire cohort, even when adjusted for molecular pathology. Gross total resection was found to be associated with longer survival in all patients and in the astrocytoma group but not in the oligodendroglioma group. Compared with subtotal resections, gross total resections resulted in a longer survival time for astrocytoma patients aged ≤ 45 years. However, there was no survival benefit from total resection in patients with astrocytoma aged > 45 years. Extensive resection benefits only a proportion of patients with WHO grade 3 IDH-mutant gliomas. Younger patients with astrocytomas had survival benefits from extensive resection. In addition to clinical characteristics (especially age), molecular pathology impacted prognosis in patients with gliomas. Our findings provide guiding information to neurosurgeons while planning surgeries.

Ultrasound for diagnosis of postpartum retained products of conception—How accurate we are?

ObjectivePostpartum retained products of conception (RPOC) can cause short- and long-term complications. Diagnosis is based on ultrasound examination and treated with hysteroscopy. This study evaluated the size of RPOC that can be related to a positive pathology result for residua.Materials and methodsThis retrospective cohort study included women who underwent hysteroscopy for postpartum RPOC diagnosed by ultrasound, 4/2014–4/2022. Demographics, intrapartum, sonographic, intraoperative, and post-operative data were retrieved. We generated a ROC curve and found 7 mm was the statistically sonographic value for positive pathology for RPOC. Data between women with sonographic RPOC ≤ 7 mm and > 7 mm were compared. Positive and negative predictive values were calculated for RPOC pathology proved which was measured by ultrasound.ResultsAmong 212 patients who underwent hysteroscopy due to suspected RPOC on ultrasound, 20 (9.4%) women had residua ≤ 7 mm and 192 (90.6%) had residua > 7 mm. The most common complaint was vaginal bleeding in 128 cases (60.4%); more so in the residua > 7 mm group (62.5% vs. 40%, p = .05). Among women with residua ≤ 7 mm, the interval from delivery to hysteroscopy was longer (117.4 ± 74.7 days vs. 78.8 ± 68.8 days, respectively; p = .02). Positive pathology was more frequent when residua was > 7 mm. PPV for diagnosis of 7 mm RPOC during pathology examination was 75.3% and NPV 50%.ConclusionsSonographic evaluation after RPOC showed that residua > 7 mm was statistically correlated with positive RPOC in pathology and PPV of 75% and NPV of 50%. Due to the high NPV and low complication rate of office hysteroscopy, clinicians should consider intervention when any RPOC are measured during sonographic examination to reduce known long-term complications.

Intraoperative predictors of appendiceal abnormalities in patients with mucinous ovarian neoplasms.

To evaluate intraoperative factors predicting appendiceal pathology during gynecologic oncology surgery for suspected mucinous ovarian neoplasms. We conducted a retrospective study on 225 patients with mucinous ovarian neoplasms who underwent surgery for an adnexal mass with concurrent appendectomy between 2000 and 2018. Regression analyses were used to evaluate intraoperative factors, such as frozen section of the ovarian mass and surgeon's impression of the appendix in predicting appendiceal pathology. Most patients (77.8%) had a normal appendix on final pathology. Abnormal appendix cases (n = 26) included: metastasis from high-grade adenocarcinoma of the ovary (n = 1), neuroendocrine tumor of the appendix (n = 4), and low-grade appendiceal mucinous neoplasms (n = 26; 23 associated with a mucinous ovarian adenocarcinoma, 2 with a benign mucinous ovarian cystadenoma, and 1 with a borderline mucinous ovarian tumor). Combining normal intraoperative appearance of the appendix with benign or borderline frozen section yielded a negative predictive value of 85.1%, with 14.9% of patients being misclassified, and 6.0% having a neuroendocrine tumor or low-grade appendiceal neoplasm. Benign or borderline frozen section of an ovarian mucinous neoplasm and normal appearing appendix have limited predictive value for appendiceal pathology. Appendectomy with removal of the mesoappendix should be considered in all cases of mucinous ovarian neoplasm, regardless of intraoperative findings.

The Hook Test Is Not Pathognomonic for Foveal Detachment of the Triangular Fibrocartilage.

Background The integrity of the foveal insertion of the triangular fibrocartilage complex (TFCC) is currently assessed by inference using the hook test. Using dry arthroscopic techniques, the primary author observed that many patients with painful distal radioulnar joint (DRUJ) instability and a positive hook test had an intact foveal insertion. This study was performed to determine whether a positive hook test is a reliable index of a tear of the foveal insertion. Technique The hook test is performed using a probe to elevate the TFCC off the ulna head toward the articular surface of the lunate. In this study, the hook test was considered positive if the TFCC could be elevated to bridge more than 80% of the space between the TFCC and the articular surface of the lunate. Patients and Methods A retrospective study was performed using the medical records and arthroscopic videos of 113 patients who had clinical signs of DRUJ instability and underwent arthroscopic surgery performed by the primary author in 2020. It was documented whether the hook test was positive or negative, whether the foveal insertion was intact, abnormal or absent, and whether there were peripheral (dorsal or volar) tears of the TFCC. Sensitivity and specificity were calculated using arthroscopic findings as the reference standard. Results The sensitivity of the hook test was found to be 100%, and the specificity was 7.0%. The positive predictive value for foveal pathology was found to be 12.3% and the negative predictive value 100%. The diagnostic accuracy of the hook test in determining the presence of foveal tears was found to be 17.7%. The diagnostic accuracy of the hook test in determining the presence of a TFCC abnormality was 99.1%. Conclusions A positive hook test is indicative of a tear of the TFCC, but it is not anatomically specific for a tear of the foveal insertion. To reliably assess the foveal insertion, it must be visualized and probed using dry arthroscopic techniques.

Social value of pathology: adapting primary health care to reduce stress and social anxiety in college students exposed to social distancing.

This article examined the impact of online education on the wellbeing and emotional health of college students. It considered the social value of stress and anxiety pathology as "normal" side effects throughout the COVID-19 lockdown. Factors appropriate for educational technology were selected and submitted for evaluation to a sample of 114 college students in a semi-structured questionnaire. This research found that educational content and delivery methods, as well as increased homework and time spent online, have potentially contributed to heightened levels of stress, depression, and social anxiety disorder among approximately one-third of students who have engaged in digital learning. The results also prove that young people were particularly susceptible to stress and social anxiety disorders during the lockdown, making them one of the most vulnerable social groups. To enhance the educational experience, several suggestions have been proposed, including adapting educational content, expanding Internet accessibility, providing appropriate homework, and adjusting schedules to accommodate students' educational capabilities. Voluntary routine mental health assessments of students, teachers, and staff and customized online counseling for vulnerable subjects are recommended as primary health care measures during online education.

Results of the European Society of Toxicologic Pathology Survey on the Use of Artificial Intelligence in Toxicologic Pathology.

The European Society of Toxicologic Pathology (ESTP) initiated a survey through its Pathology 2.0 workstream in partnership with sister professional societies in Europe and North America to generate a snapshot of artificial intelligence (AI) usage in the field of toxicologic pathology. In addition to demographic information, some general questions explored AI relative to (1) the current status of adoption across organizations; (2) technical and methodological aspects; (3) perceived business value and finally; and (4) roadblocks and perspectives. AI has become increasingly established in toxicologic pathology with most pathologists being supportive of its development despite some areas of uncertainty. A salient feature consisted of the variability of AI awareness and adoption among the responders, as the spectrum extended from pathologists having developed familiarity and technical skills in AI, to colleagues who had no interest in AI as a tool in toxicologic pathology. Despite a general enthusiasm for these techniques, the overall understanding and trust in AI algorithms as well as their added value in toxicologic pathology were generally low, suggesting room for the need for increased awareness and education. This survey will serve as a basis to evaluate the evolution of AI penetration and acceptance in this domain.

Current Utilization of Electron Microscopy in the Pediatric Pathology Setting: A Survey by the SPP Practice Committee.

Electron microscopy (EM), once an important component in diagnosing pediatric diseases, has experienced a decline in its use. To assess the impact of this, pediatric pathology practices were surveyed regarding EM services. The Society of Pediatric Pathology Practice Committee surveyed 113 society members from 74 hospitals. Settings included 36 academic tertiary, 32 free-standing children's, and 6 community hospitals. Over 60% maintained in-house EM services and had more than 2 pathologists interpreting EM while reporting a shortage of EM technologists. Freestanding children's hospitals had the most specimens (100-200 per year) and more diverse specimen types. Hospitals with fewer than 50 yearly specimens often used reference laboratories. Seventeen had terminated all in-house EM services. Challenges included decreasing caseloads due to alternative diagnostic methods, high operating costs, and shortages of EM technologists and EM-proficient pathologists. Kidney, liver, cilia, heart, and muscle biopsies most often required EM. Lung/bronchoalveolar lavage, tumor, skin, gastrointestinal, nerve, platelet, and autopsy samples less commonly needed EM. The survey revealed challenges in maintaining EM services but demonstrated its sustained value in pediatric pathology. Pediatric pathologists may need to address the centralization of services and training to preserve EM diagnostic proficiency among pathologists who perform ultrastructural interpretations.

Critical value in surgical pathology: evaluating the current status in a multicenter study

BackgroundThe concept of critical value is not evident in surgical pathology, and there is no established protocol for determining, reporting, and documenting these results.Materials and methodsA questionnaire was designed regarding critical value in surgical pathology, and all pathologists and some clinicians from five laboratories were asked to participate through an invitation link. The most important items were selected, and all pathologists were instructed to follow a standard operating procedure to deal with critical results for a year.ResultsA total of 43 pathologists and 44 non-pathologists participated in the study. Some critical or unexpected items were selected. Most participants agreed that the optimal time to announce critical reports is within 24 h of establishing the final diagnosis, and a phone call was the most dependable communication option. In addition, the most qualified recipients were the attending physicians. Therefore, a written policy was implemented for a year. One hundred seventy-seven critical or unexpected cases (0.5%) were detected. Mucormycosis and cytomegalovirus (CMV) were the most frequent critical cases.ConclusionThere are no set criteria for critical items or the reporting process in surgical pathology. It is possible to establish more uniform norms for reporting these cases by boosting pertinent research efforts and recruiting more pathologists and physicians. Additionally, it is advised that each medical facility compile its own unique critical or unexpected diagnosis list.

Abstract 3359: Sensitive detection of locoregional MRD after head and neck cancer surgery

Abstract Background: Plasma cell-free DNA (cfDNA) has low sensitivity to detect locoregional molecular residual disease (MRD) immediately after surgery for limited-stage head and neck cancer. To enhance locoregional MRD sensitivity, we utilize a novel biofluid proximal to the primary tumor: the serosanguinous fluid collected by surgical drains inserted into the wound bed following regional lymph node dissection. We demonstrate that cancer-associated cfDNA in the surgical drain fluid (SDF) is a sensitive biomarker of locoregional MRD detection, risk stratification, and prognostication. Methods: We extracted DNA from 168 SDFs, 48 paired plasmas, and 44 tumor specimens collected 24 hours after surgery from 90 patients: 74 HPV (+) oropharyngeal cancers (OPC), 8 HPV (-) oral cancers, 2 thyroid cancers, and 6 benign neck pathologies. SDFs were also collected at 0, 6, 12, and 24 hours after surgery from 11 HPV (+) patients. We applied TaqMan qPCR to our specimens to quantify cell-free HPV (cf-HPV), a proxy for cancer-associated cfDNA in HPV (+) malignancies. We then measured the association between cf-HPV and extranodal extension (ENE), AJCC 8 staging, and established clinical and pathological risk criteria from 4 HPV (+) OPC clinical trials. We validated our findings using HPV next-generation sequencing. We also compared the predictive value of high-risk pathology with cf-HPV MRD for HPV (+) OPC recurrences. Lastly, we developed a second assay for cell-free BRAF V600E (cf-V600E) in thyroid cancer SDF. Results: Serially collected SDF revealed cf-HPV decreased continuously from 0 to 24 hours postoperative, and that the 24-hour timepoint stratified detectable versus undetectable persistent residual disease. At 24 hours, SDF was significantly more enriched with cf-HPV compared to plasma (P &amp;lt; 0.0001). In a subset of 9 patients, HPV genotype and detection in SDF were 100% concordant between NGS and PCR. Strikingly, SDF cf-HPV was 11-fold higher in pN2 patients versus pN1/N0 (P = 0.02) and 15-fold higher in cases with ENE (P = 0.003), suggesting SDF reflects aggressive nodal pathology and captures locoregional MRD. When we classified our patients according to established clinical and pathological risk criteria, we found significantly higher SDF cf-HPV among high-risk patients (AUC = 0.77). Crucially, in HPV (+) patients treated with surgery alone, SDF MRD detected 100% of locoregional recurrences, while plasma MRD and high-risk pathology detected 0%. Lastly, as proof of concept, we demonstrated SDF cf-V600E detection in the context of high-risk thyroid cancer. Conclusions: Surgical drain fluid cancer-associated cfDNA is a novel minimally invasive biomarker. Our SDF assay was strongly associated with high-risk criteria and detected locoregional relapse with 100% sensitivity compared to 0% in plasma. Our data suggest that SDF liquid biopsy is ultra-sensitive and has the potential to inform postoperative molecular-based risk stratification. Citation Format: Noah Earland, Ricardo J. Ramirez, Sophie P. Gerndt, Peter K. Harris, Andrew I. Hearn, Matthew Inkman, Jeffrey J. Szymanski, Nick Semenkovich, Benjamin M. Wahle, Zhongping Xu, Kevin Chen, Jin Zhang, Jose P. Zevallos, Aadel A. Chaudhuri. Sensitive detection of locoregional MRD after head and neck cancer surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3359.

The Significance of Serum C-Reactive Protein and Neutrophil-Lymphocyte Ratio in Predicting the Diagnostic Outcomes of Renal Mass Biopsy Procedure.

This study aimed to investigate the predictive role of serum C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) on renal mass biopsy outcomes. A total of 71 patients with suspected kidney masses who underwent renal mass biopsy procedure between January 2017 and January 2021 were retrospectively evaluated. Pathological results after the procedure were obtained and pre-procedural serum CRP and NLR levels were extracted from the patients' data. The patients were grouped into benign and malignant pathology groups according to the histopathology results. The parameters were compared between the groups. Diagnostic role of the parameters in terms of sensitivity, specificity, and positive and negative predictive values was also determined. Additionally, Pearson correlation analysis, and univariate and multivariate cox proportional hazard regression analyses were also performed to investigate the above association with tumor diameter and pathology results, respectively. At the end of the analyses, a total of 60 patients had malignant pathology on histopathological investigations of the mass biopsy specimens, whereas the remaining 11 patients had a benign pathological diagnosis. Significantly higher CRP and NLR levels were detected in the malignant pathology group. The parameters positively correlated with the malignant mass diameter, as well. Serum CRP and NLR determined the malignant masses before the biopsy with sensitivity and specificity of 76.6 and 81.8%, and 88.3 and 45.4%, respectively. Moreover, univariate and multivariate analyses showed that serum CRP level had a significant predictive value for malignant pathology (HR: 0.998, 95% CI: 0.940-0.967, P < 0.001 and HR: 0.951, 95% CI: 0.936-0.966, P < 0.001, respectively). In conclusion, serum CRP and NLR levels were significantly different in patients with malignant pathology after renal mass biopsy compared to the patients with benign pathology. Serum CRP level, in particular, diagnosed malignant pathologies with acceptable sensitivity and specificity values. Additionally, it had a substantial predictive role in determining the malign masses prior the biopsy. Therefore, pre-biopsy serum CRP and NLR levels may be used to predict the diagnostic outcomes of renal mass biopsy in clinical practice. Further studies with larger cohorts can prove our findings in the future.